The long-range objective of research outlined in this proposal is to delineate mechanisms essential for a clear understanding of the biochemical correlates of alcoholism. Biosynthetic processes responsible for the adaptive increase in ethanol and oxygen uptake in perfused livers of normal and ethanol-treated rats will be studied in detail. Moreover, mechanisms responsible for the development of tolerance and physical dependence to alcohol in the central nervous system will be probed. The role of cyclic nucleotides in these processes will be studied exhaustively.